IU Indianapolis ScholarWorks :: Browsing by Subject "Epilepsy"

Browsing by Subject "Epilepsy"

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A Literature Review of Similarities Between and Among Patients With Autism Spectrum Disorder and Epilepsy
(Springer Nature, 2023-01-18) Assuah, Freda B.; Emanuel, Bryce; Lacasse, Brianna M.; Beggs, John; Lou, Jennie; Motta, Francis C.; Nemzer, Louis R.; Worth, Robert; Cravens, Gary D.; Mathematical Sciences, School of Science
Autism spectrum disorder (ASD) has been shown to be associated with various other conditions, and most commonly, ASD has been demonstrated to be linked to epilepsy. ASD and epilepsy have been observed to exhibit high rates of comorbidity, even when compared to the co-occurrence of other disorders with similar pathologies. At present, nearly one-half of the individuals diagnosed with ASD also have been diagnosed with comorbid epilepsy. Research suggests that both conditions likely share similarities in their underlying disease pathophysiology, possibly associated with disturbances in the central nervous system (CNS), and may be linked to an imbalance between excitation and inhibition in the brain. Meanwhile, it remains unclear whether one condition is the consequence of the other, as the pathologies of both disorders are commonly linked to many different underlying signal transduction mechanisms. In this review, we aim to investigate the co-occurrence of ASD and epilepsy, with the intent of gaining insights into the similarities in pathophysiology that both conditions present with. Elucidating the underlying disease pathophysiology as a result of both disorders could lead to a better understanding of the underlying mechanism of disease activity that drives co-occurrence, as well as provide insight into the underlying mechanisms of each condition individually.
Boricua Founder Variant in FRRS1L Causes Epileptic Encephalopathy With Hyperkinetic Movements
(Sage, 2021) Abdelmoumen, Imane; Jimenez, Sandra; Valencia, Ignacio; Melvin, Joseph; Legido, Agustin; Diaz-Diaz, Mayela M.; Griffith, Christopher; Massingham, Lauren J.; Yelton, Melissa; Rodríguez-Hernández, Janice; Schnur, Rhonda E.; Walsh, Laurence E.; Cristancho, Ana G.; Bergqvist, Christina A.; McWalter, Kirsty; Mathieson, Iain; Belbin, Gillian M.; Kenny, Eimear E.; Ortiz-Gonzalez, Xilma R.; Schneider, Michael C.; Neurology, School of Medicine
Objective: To describe a founder mutation effect and the clinical phenotype of homozygous FRRS1L c.737_739delGAG (p.Gly246del) variant in 15 children of Puerto Rican (Boricua) ancestry presenting with early infantile epileptic encephalopathy (EIEE-37) with prominent movement disorder. Background: EIEE-37 is caused by biallelic loss of function variants in the FRRS1L gene, which is critical for AMPA-receptor function, resulting in intractable epilepsy and dyskinesia. Methods: A retrospective, multicenter chart review of patients sharing the same homozygous FRRS1L (p.Gly246del) pathogenic variant identified by clinical genetic testing. Clinical information was collected regarding neurodevelopmental outcomes, neuroimaging, electrographic features and clinical response to antiseizure medications. Results: Fifteen patients from 12 different families of Puerto Rican ancestry were homozygous for the FRRS1L (p.Gly246del) pathogenic variant, with ages ranging from 1 to 25 years. The onset of seizures was from 6 to 24 months. All had hypotonia, severe global developmental delay, and most had hyperkinetic involuntary movements. Developmental regression during the first year of life was common (86%). Electroencephalogram showed hypsarrhythmia in 66% (10/15), with many older children evolving into Lennox-Gastaut syndrome. Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI). Conclusions: We describe the largest cohort to date of patients with epileptic encephalopathy. We estimate that 0.76% of unaffected individuals of Puerto Rican ancestry carry this pathogenic variant due to a founder effect. Children homozygous for the FRRS1L (p.Gly246del) Boricua variant exhibit a very homogenous phenotype of early developmental regression and epilepsy, starting with infantile spasms and evolving into Lennox-Gastaut syndrome with hyperkinetic movement disorder.
Central and Peripheral Inflammation: A Common Factor Causing Addictive and Neurological Disorders and Aging-Related Pathologie
(MDPI, 2023-06-13) Escobar, Angélica P.; Bonansco, Christian; Cruz, Gonzalo; Dagnino-Subiabre, Alexies; Fuenzalida, Marco; Negrón, Ignacio; Sotomayor-Zárate, Ramón; Martínez-Pinto, Jonathan; Jorquera, Gonzalo; Anatomy, Cell Biology and Physiology, School of Medicine
Many diseases and degenerative processes affecting the nervous system and peripheral organs trigger the activation of inflammatory cascades. Inflammation can be triggered by different environmental conditions or risk factors, including drug and food addiction, stress, and aging, among others. Several pieces of evidence show that the modern lifestyle and, more recently, the confinement associated with the COVID-19 pandemic have contributed to increasing the incidence of addictive and neuropsychiatric disorders, plus cardiometabolic diseases. Here, we gather evidence on how some of these risk factors are implicated in activating central and peripheral inflammation contributing to some neuropathologies and behaviors associated with poor health. We discuss the current understanding of the cellular and molecular mechanisms involved in the generation of inflammation and how these processes occur in different cells and tissues to promote ill health and diseases. Concomitantly, we discuss how some pathology-associated and addictive behaviors contribute to worsening these inflammation mechanisms, leading to a vicious cycle that promotes disease progression. Finally, we list some drugs targeting inflammation-related pathways that may have beneficial effects on the pathological processes associated with addictive, mental, and cardiometabolic illnesses.
Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice
(Public Library of Science (PLoS), 2016) Ping, Xingjie; Jin, Xiaoming; Department of Anatomy & Cell Biology, IU School of Medicine
Posttraumatic epilepsy (PTE) usually develops in a small percentage of patients of traumatic brain injury after a varying latent period. Modeling this chronic neurological condition in rodents is time consuming and inefficient, which constitutes a significant obstacle in studying its mechanism and discovering novel therapeutics for its prevention and treatment. Partially isolated neocortex, or undercut, is known to induce cortical hyperexcitability and epileptiform activity in vitro, and has been used extensively for studying the neurophysiological mechanism of posttraumatic epileptogenesis. However, whether the undercut lesion in rodents causes chronic epileptic seizures has not been systematically characterized. Here we used a miniature telemetry system to continuously monitor electroencephalography (EEG) in adult C57BL mice for up to 3 months after undercut surgery. We found that 50% of animals developed spontaneous seizures between 16-50 days after injury. The mean seizure duration was 8.9±3.6 seconds, and the average seizure frequency was 0.17±0.17 times per day. There was no progression in seizure frequency and duration over the recording period. Video monitoring revealed behavioral arrests and clonic limb movement during seizure attacks. A pentylenetetrazol (PTZ) test further showed increased seizure susceptibility in the undercut mice. We conclude that undercut lesion in mice is a model of chronic PTE that involves spontaneous epileptic seizures.
Comorbidity of attention deficit hyperactivity disorder in a patient with epilepsy: Staring down the challenge of inattention versus nonconvulsive seizures
(Elsevier, 2024-02-01) Miller, Derryl J.; Komanapalli, Hannah; Dunn, David W.; Neurology, School of Medicine
Epilepsy is a heterogeneous disorder of recurrent seizures which often is comorbid with anxiety, depression, attention deficit hyperactivity disorder (ADHD), intellectual disability (ID), and other psychiatric manifestations. Treating both epilepsy and behavioral symptoms from psychiatric disorders can result in polypharmacy with interactions of medications leading to both worsened efficacy of antiseizure medications due to psychotropic effects and worsening of psychiatric symptoms due to antiseizure medication side effects. We aim to suggest pragmatic strategies for the neurologist in the diagnosis and management of comorbid ADHD in patients with epilepsy based on the International League Against Epilepsy (ILAE) Pediatric Commission guidelines and additional literature review. The screening tool of choice for the symptoms of ADHD is validated in the country of practice and written in the language of the family, though various screening tools and advantages and disadvantages of each will be discussed. Once ADHD is diagnosed, recent safety data suggest that Methylphenidate, Amphetamine, and Atomoxetine are generally safe for patients with epilepsy. We present a case of a child with epilepsy and ADHD and discuss the clinical signs, symptoms, and strategies for treatment as well as when to refer to child psychiatry.
Connectomic profiling and Vagus nerve stimulation Outcomes Study (CONNECTiVOS): a prospective observational protocol to identify biomarkers of seizure response in children and youth
(BMJ, 2022-04-08) Siegel, Lauren; Yan, Han; Warsi, Nebras; Wong, Simeon; Suresh, Hrishikesh; Weil, Alexander G.; Ragheb, John; Wang, Shelly; Rozzelle, Curtis; Albert, Gregory W.; Raskin, Jeffrey; Abel, Taylor; Hauptman, Jason; Schrader, Dewi V.; Bollo, Robert; Smyth, Matthew D.; Lew, Sean M.; Lopresti, Melissa; Kizek, Dominic J.; Weiner, Howard L.; Fallah, Aria; Widjaja, Elysa; Ibrahim, George M.; Neurological Surgery, School of Medicine
Introduction: Vagus nerve stimulation (VNS) is a neuromodulation therapy that can reduce the seizure burden of children with medically intractable epilepsy. Despite the widespread use of VNS to treat epilepsy, there are currently no means to preoperatively identify patients who will benefit from treatment. The objective of the present study is to determine clinical and neural network-based correlates of treatment outcome to better identify candidates for VNS therapy. Methods and analysis: In this multi-institutional North American study, children undergoing VNS and their caregivers will be prospectively recruited. All patients will have documentation of clinical history, physical and neurological examination and video electroencephalography as part of the standard clinical workup for VNS. Neuroimaging data including resting-state functional MRI, diffusion-tensor imaging and magnetoencephalography will be collected before surgery. MR-based measures will also be repeated 12 months after implantation. Outcomes of VNS, including seizure control and health-related quality of life of both patient and primary caregiver, will be prospectively measured up to 2 years postoperatively. All data will be collected electronically using Research Electronic Data Capture. Ethics and dissemination: This study was approved by the Hospital for Sick Children Research Ethics Board (REB number 1000061744). All participants, or substitute decision-makers, will provide informed consent prior to be enrolled in the study. Institutional Research Ethics Board approval will be obtained from each additional participating site prior to inclusion. This study is funded through a Canadian Institutes of Health Research grant (PJT-159561) and an investigator-initiated funding grant from LivaNova USA (Houston, TX; FF01803B IIR).
Cortical stimulation for treatment of neurological disorders of hyperexcitability: a role of homeostatic plasticity
(Wolters Kluwer, 2019-01) Chai, Zhi; Ma, Cungen; Jin, Xiaoming; Anatomy and Cell Biology, IU School of Medicine
Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.
Critical and Ictal Phases in Simulated EEG Signals on a Small-World Network
(Frontiers Media, 2021-01-08) Nemzer, Louis R.; Cravens, Gary D.; Worth, Robert M.; Motta, Francis; Placzek, Andon; Castro, Victor; Lou, Jennie Q.; Mathematical Sciences, School of Science
Healthy brain function is marked by neuronal network dynamics at or near the critical phase, which separates regimes of instability and stasis. A failure to remain at this critical point can lead to neurological disorders such as epilepsy, which is associated with pathological synchronization of neuronal oscillations. Using full Hodgkin-Huxley (HH) simulations on a Small-World Network, we are able to generate synthetic electroencephalogram (EEG) signals with intervals corresponding to seizure (ictal) or non-seizure (interictal) states that can occur based on the hyperexcitability of the artificial neurons and the strength and topology of the synaptic connections between them. These interictal simulations can be further classified into scale-free critical phases and disjoint subcritical exponential phases. By changing the HH parameters, we can model seizures due to a variety of causes, including traumatic brain injury (TBI), congenital channelopathies, and idiopathic etiologies, as well as the effects of anticonvulsant drugs. The results of this work may be used to help identify parameters from actual patient EEG or electrocorticographic (ECoG) data associated with ictogenesis, as well as generating simulated data for training machine-learning seizure prediction algorithms.
Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome
(Elsevier, 2021-11) Weerts, Marjolein J.A.; Lanko, Kristina; Guzmán-Vega, Francisco J.; Jackson, Adam; Ramakrishnan, Reshmi; Cardona-Londoño, Kelly J.; Peña-Guerra, Karla A.; van Bever, Yolande; van Paassen, Barbara W.; Kievit, Anneke; van Slegtenhorst, Marjon; Allen, Nicholas M.; Kehoe, Caroline M.; Robinson, Hannah K.; Pang, Lewis; Banu, Selina H.; Zaman, Mashaya; Efthymiou, Stephanie; Houlden, Henry; Järvelä, Irma; Lauronen, Leena; Määttä, Tuomo; Schrauwen, Isabelle; Leal, Suzanne M.; Ruivenkamp, Claudia A.L.; Barge-Schaapveld, Daniela Q.C.M.; Peeters-Scholte, Cacha M.P.C.D.; Galehdari, Hamid; Mazaheri, Neda; Sisodiya, Sanjay M.; Harrison, Victoria; Sun, Angela; Thies, Jenny; Pedroza, Luis Alberto; Lara-Taranchenko, Yana; Chinn, Ivan K.; Lupski, James R.; Garza-Flores, Alexandra; McGlothlin, Jeffery; Yang, Lin; Huang, Shaoping; Wang, Xiaodong; Jewett, Tamison; Rosso, Gretchen; Lin, Xi; Mohammed, Shehla; Merritt, J. Lawrence, II.; Mirzaa, Ghayda M.; Timms, Andrew E.; Scheck, Joshua; Elting, Mariet W.; Polstra, Abeltje M.; Schenck, Lauren; Ruzhnikov, Maura R.Z.; Vetro, Annalisa; Montomoli, Martino; Guerrini, Renzo; Koboldt, Daniel C.; Mihalic Mosher, Theresa; Pastore, Matthew T.; McBride, Kim L.; Peng, Jing; Pan, Zou; Willemsen, Marjolein; Koning, Susanne; Turnpenny, Peter D.; de Vries, Bert B.A.; Gilissen, Christian; Pfundt, Rolph; Lees, Melissa; Braddock, Stephen R.; Klemp, Kara C.; Vansenne, Fleur; van Gijn, Marielle E.; Quindipan, Catherine; Deardorff, Matthew A.; Hamm, J. Austin; Putnam, Abbey M.; Baud, Rebecca; Walsh, Laurence; Lynch, Sally A.; Baptista, Julia; Person, Richard E.; Monaghan, Kristin G.; Crunk, Amy; Keller-Ramey, Jennifer; Reich, Adi; Elloumi, Houda Zghal; Alders, Marielle; Kerkhof, Jennifer; McConkey, Haley; Haghshenas, Sadegheh; Maroofian, Reza; Sadikovic, Bekim; Banka, Siddharth; Arold, Stefan T.; Barakat, Tahsin Stefan; Medical and Molecular Genetics, School of Medicine
Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.
Deoxyhypusine synthase deficiency syndrome zebrafish model: aberrant morphology, epileptiform activity, and reduced arborization of inhibitory interneurons
(Springer Nature, 2024-09-27) Shojaeinia, Elham; Mastracci, Teresa L.; Soliman, Remon; Devinsky, Orrin; Esguerra, Camila V.; Crawford, Alexander D.; Biology, School of Science
DHPS deficiency syndrome is an ultra-rare neurodevelopmental disorder (NDD) which results from biallelic mutations in the gene encoding the enzyme deoxyhypusine synthase (DHPS). DHPS is essential to synthesize hypusine, a rare amino acid formed by post-translational modification of a conserved lysine in eukaryotic initiation factor 5 A (eIF5A). DHPS deficiency syndrome causes epilepsy, cognitive and motor impairments, and mild facial dysmorphology. In mice, a brain-specific genetic deletion of Dhps at birth impairs eIF5AHYP-dependent mRNA translation. This alters expression of proteins required for neuronal development and function, and phenotypically models features of human DHPS deficiency. We studied the role of DHPS in early brain development using a zebrafish loss-of-function model generated by knockdown of dhps expression with an antisense morpholino oligomer (MO) targeting the exon 2/intron 2 (E2I2) splice site of the dhps pre-mRNA. dhps knockdown embryos exhibited dose-dependent developmental delay and dysmorphology, including microcephaly, axis truncation, and body curvature. In dhps knockdown larvae, electrophysiological analysis showed increased epileptiform activity, and confocal microscopy analysis revealed reduced arborisation of GABAergic neurons. Our findings confirm that hypusination of eIF5A by DHPS is needed for early brain development, and zebrafish with an antisense knockdown of dhps model features of DHPS deficiency syndrome.

Browsing by Subject "Epilepsy"

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